0,0,0{40 ,0{40 -Tetraalkyl, 0,0{40 -vinylenedi-p-phenylene phosphorothioates

ABSTRACT

This invention relates to 0,0,0&#39;&#39;,0&#39;&#39;-tetraalkyl(C1-C4) 0,0&#39;&#39;vinylenedi-p-phenylene phosphorothioates, compositions containing said compounds as the active component and to methods of use thereof. The compounds are useful in controlling siphonaptera infestations.

United States Patent [191 Levy et al.

[ Sept. 23, 19 75 0,0,0,0-TETRAALKYL,

0,0'-VINYLENEDI-P-PHENYLENE PHOSPHOROTHIOATES [75] Inventors: Stephen David Levy, Trenton;

Gordon Paul Poeschel, Pennington; Michael Stanley Scrider, South Bound Brook, all of NJ.

[73] Assignee: American Cyanamid Company,

Stamford, Conn.

[22 Filed: Apr. 11, 1974 [2i] Appl. 190.; 460,257

[52] US. Cl. 260/930; 424/206 [51] Int. Cl. C07F 9/165;A01N 9/36 [58] Field of Search 260/930 [56] References Cited UNITED STATES PATENTS 2,643,265 6/1953 Toy 260/930 FOREIGN PATENTS OR APPLICATIONS 674,087 6/1952 United Kingdom 260/930 Primary Examiner-Ant0n H. Sutto Attorney, Agent, or FirmErnest Y. Miller 6 Claims, No Drawings 0,0,0,O-TETRAALKYL, 0,0-VINYLENEDI-P-PHENYLENE PHOSPI-IOROTHIOATES DESCRIPTION OF THE INVENTION The present invention relates to compounds of the formula:

S S ll wherein R is alkyl C such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and the like, to compositions containing said esters as the active ingredient, and to methods for controlling Siphonaptera therewith.

The compounds of the above formula may be prepared by reacting 4,4'-dihydroxystilbene with an 0,0- di(alkyl C d-thiophosphoryl halide. The reaction may be illustrated as follows:

S ll HO CH=CH OH 2(RO) P-Y acid acceptor organic solvent S w S ll ll (RO),PO .CH=CH OP(OR)2 wherein Y is halogen, such as chloro or bromo, and R is alkyl C The starting materials are well known. Thus, the 4,-4'-dihydroxystilbene is a mixture of cis and trans isomers usually with the trans isomer predominating, obtainable by several procedures according to Beilstein Organisclie Che mie Band VI, pg. l022. The isomers can be separated by methods well known in the Chemical Arts and when the pure isomer is used in the reaction, the corresponding isomeric form will be obtained in the final product. The dialkyl thiophosphoryl halides are described in a multiplicity of references. The reaction is conducted in an organic solvent such as, for example,the oxygenated solvents t-butyl alcohol, methyl isobutyl ketone, acetone, methyl ethyl ketone or diethyl ether, hydrocarbon solvents'such' as benzene, toluene, xylene or chloroform, and the like,

in the presence of an acid acceptor such as, for example, potassium t-butyl alkoxide, sodium methoxide, so-

dium hydroxide, sodium carbonate, pyridine, triethylamine, and the like. The reaction may also be conducted in the absence of an acid-acceptor if conditions are such that the acid released by the reaction is efficiently removed as by distillation. A satisfactory production of the above-described compounds are ob- The compounds of this invention have been found to be highly siphonaptericidal and effective against Ctenocephalides spp. and are useful in controlling flea infestations of domestic'warm-blooded animals, particularly cats and dogs.

When the compounds of this invention are used as control agentsfor'Siphonaptera in insecticidal and larvicidal amounts, such compounds may be brought into contact with adult insect, or larvae of said insect, or

they may be applied to the habitat, breeding grounds and/or dietary media of said insects or larvae, that is organic matter, living or dead, which forms their food, or

to the animal host of the insect.

It is a good practice to formulate the compounds of this invention with a conventional solid or liquid diluout and a formulation aid. As siphonaptericides they may be formulated as granulars, dusts, dust concentrates, wettable powders, emulsifiable concentrates, and the like. They may also be incorporated in baits for adult fleas or they may be incorporated in a plastic such as a polyvinyl chloride, and made up in the form of a collar and placed around the neck of an animal. I

Useful liquid diluents in which the compounds of this invention may bedissolved or suspended include, for example, water, xylene, benzene, keto alcohols such as diacetone alcohol, lower alcohols C -C fuel oil, esters and the like, either with or without a surfactant. For application, the resulting solution or suspension can be further diluted with either water or an organic diluent, such as deodorized kerosene. Concentrations in the range from 5% to 95% active ingredient by weight are generally suitable for the initial solution or suspension. When diluted for application, suitable solutions and suspensions contain the active ingredient in concentrations from 1% to about 90% by weight.

The term suspension, as employed herein, includes dispersions of either solid particles or immiscible liquid droplets. The latter type of dispersion is more particularly referred to when-fully dispersed as an emulsion.

In the preparation of a dispersion of solid particles, it is preferable to include a dispersing agent to promote the separation of deflocculation of the particles of the active ingredient. Examples of suchdispersing agents are sodium lignosulfonate, calcium lignosulfonate, the

sodium salt of a naphthalenesulfonic acid condensed with formaldehyde, the sodium salts of polymeric carboxylic acids, the sodium salts of carboxylated polyelectrolytes, and the like.

Dusts or dust concentrates, can be prepared by grinding together an inert solid diluent such as attapulgite,

kaolin, walnut shell flour, diatomaceous earth, ground corn cob grites, or ground coconut shell, and the active ingredient, where such active ingredient is in solid form. Where the active ingredient is a liquid, it may be sprayed on the carrier and thoroughly mixed with it or it may be dissolved in a solvent such as acetone or xylene, and the solution sprayed on the solid carrier. Dusts usually contain from about 1% to 15% by weight of active ingredient, whereas concentrates may contain from about 16% to about by weight of the active material.

Wettable powders are prepared in the same fashion as dust concentrates, excepting that they contain from 5% to compound and about 10% to 20% by weight of a wetting agent and 5% to 10% by weight of'a dispersing agent are included. Examples of such wetting agents are polyoxyethylene derivatives, sodium N-methyl-N-oleoyl taurate, alkyl phenoxy polyoxyethylene ethanol, and the like.

It is obvious that dusts can also be prepared from wettable powders. For example, to prepare a dust, by weight of a 50% wettable powder can be blended with about 80% by weight of a solid carrier, such as kaolin. Suitable equipment for such preparations are ribbon-type blenders and double-cone blenders. It is also obvious that the concentration of active ingredient in such dust formulations can readily be varied by adjusting the amount of wettable powder and carrier used. Such dusts will generally vary between about 1% to 15% by weight of active ingredient, although higher or lower concentrations may also be prepared.

A granular formulation can be prepared by blending a small amount, i.e., about 0.3% by weight, of a fused collodial silica with about 5.6% by weight of the active ingredient and airmilling the mixture to a uniform blend. Silica sand, about 85.7% by weight, is then placed in a blender along with about 0.7% by weight of calcium-sodium lignin sulfonate powder and 4.2% of a 1% aqueous solution of calcium-sodium lignin sulfonate. The mixture is blended and then 3.5% by weight of synthetic calcium silicate is added. The mixture is permitted -to continue blending for several minutes until the finished product is uniformly coated and free flowing. It is, of course, obvious that the amount of active ingredient in the formulated granular product can be widely varied. This simply requires appropriate adjustment of the amount of granular carrier used and/or adjuvants added. It is likewise obvious that sorptive granular carriers, as well as nonsorptive carriers, can be employed in the preparation of the granular formulations.

The compounds of the present invention may also be prepared as emulsifiable concentrates by dissolving or dispersing about 10% to 75% by weight of the active compound in a suitable solvent or carrier such as a petroleum distillate having a minimum aromatic content of 85% and admixing therewith about 10% by weight of an emulsifier such as polyoxyethylene derivatives and blends with alkyl aryl sulfonates. These concentrates are also generally dispersed in water or other suitable solvent for application.

The application of the compounds of this invention in the form of an emulsion of the oil-in-water type, or of the water-in-oil (invert) type may also be carried out. The preferred oil-in-water type may be formed by slowly admixing an emulsifiable concentrate with water containing an emulsifing agent.

Wettable powders and emulsifiable concentrates are particularly useful since they can be diluted with water and applied as dilute liquid sprays to an infested area, for which protection is sought, or they may be sprayed on or applied topically as by pour-on to animals which are to be protected from attack. In the latter situation the dilute liquid formulation may also be applied by dipping.

Field application of the compounds of this invention to animals and infested areas, may be made by conventional equipment, such as power dusters, boom and hand sprayers, spray dusters, spray races and the like.

In the practice of this invention control of Siphonaptera can be effected by thoroughly spraying an infested animal with an aqueous dispersion containing from 0.1% active ingredient w/v to 10.0% active ingredient w/v 0.1% active ingredient w/v contains 1.0 gram of active ingredient per liter); each animal is sprayed with from 10 ml. to 200 ml. of solution.

Preferentially, application to dogs and cats to control fleas can be effected by spraying each animal with aqueous solutions containing from 0.355% to 10% (w/v) active ingredient to provide from 1.25 milligrams to milligrams of active material per kilogram of body weight.

Application to dogs and cats to control fleas can also be effected by treating each animal with a dust containing about 2% active ingredient to provide from 10 milligrams to 120 milligrams of active ingredient per kilogram of body weight.

SPECIFIC DISCLOSURE In order that the present invention may be more fully understood, the following examples are given primarily by way of illustration. No specific details or enumerations contained therein should be construed as limitations on the present invention, except insofar as they appear in the claims. All parts and percentages are by weight unless otherwise specifically designated.

EXAMPLE 1 Preparation of 0,0,0',0'-Tetramethyl 0,0'-vinylenedi-p-phenylene phosphorothioate 10.6 grams (0.05 mole) of 4,4'-dihydroxystilbene is slurried in 150 ml. of tertiary butyl alcohol at 70C. and 17.66 grams (0.11 mole) of 0,0-dimethylphosphorochloridothioate is added thereto. An amount of 11.2 grams (0.10 mole) of potassium tertiary butyl alcoholate in 100 ml. of tertiary butyl alcoholate in 100 ml. of tertiary butyl alcohol is added to the reaction mixture and the temperature is raised to 75C. The reaction mixture is held at 75C. for 15 minutes and then concentrated to obtain a residue which is dissolved in 250 ml. of diethyl ether. The ethereal solution is extracted successively with water, 5% aqueous potassium hydroxide, dilute hydrochloric acid and water saturated with sdoium chloride. The ethereal solution is then concentrated to obtain 18.9 grams of a white solid which on recrystallization from 250 mls. of boiling isopropyl a1- cohol yields 12.4 grams of white solid, melting point 1 121 13C. This material is then slurried in 200 ml. of hexane and heated to reflux. About ml. of benzene are slowly added to dissolve any insolubles and the solution is filtered and then cooled to room temperature. The precipitate is separated by filtration and dried to obtain 10.1 grams of material, melting point 113.5114C., which is homogeneous by thin layer chromatography. Analysis Calculated for C H O P S (in C, 46.95; H, 4.82; P, 13.45; S, 13.93. Found: C, 47.16; H, 4.96; P, 13.64; S, 14.04.

Employing the same procedure and substituting 0,0- diethylphosphorochloridothioate for phosphorochloridothioate yields 0,0, 0,0-tetraethyl 0,0-vinylenedi-p-phenylene phosphorothioate.

Similarly, substituting 0,0-dipropyl phosphorochloridate 0,0-diisopropyl phosphorochloridothioate for 0,0- dimethyl phosphorochloridothioate yields the corresponding 0,0,0 ',0 '-tetrapropyl 0,0'-vinylenedi-p-phenylene phosphate and 0,0,0',0'- tetraisopropyl 0,0-vinylenedi-p-phenylenephosphorothioate.

0,0-dimethyl Using as starting material trans 4,4-dihydroxystilbene or cis 4,4'-dihydroxystilbene, the corresponding trans or cis product of the invention is obtained.

EXAMPLE 2 Siphonaptericidal Activity nocephalides felis are sprayed for seconds with an acetone/water solution containing 1.0 ppm. of the test compound. After this treatment, the fleas are maintained for 48 hours at room temperature and 80+% relative humidity. At the end of this period, the fleas are examined and mortality counts made. With the abovenamed composition, which is representative of the compounds disclosed, 100% mortality is obtained.

We claim: 1. A compound selected from those of the formula:

wherein R is alkyl C -C and trans and cis isomer thereof.

2. A compound according to claim 1 of the formula:

wherein R is alkyl C,C

3. A compound according to claim 1 of the formula:

wherein R is alkyl C -C 4. The compound according to claim 1 wherein R is methyl.

5. The compound according to claim 1 of the for- 6. The compound according to claim 1 of the formula: 

1. A COMPOUND SELECTED FROM THOSE OF THE FORMULA:
 2. A compound according to claim 1 of the formula:
 3. A compound according to claim 1 of the formula:
 4. The compound according to claim 1 wherein R is methyl.
 5. The compound according to claim 1 of the formula:
 6. The compound according to claim 1 of the formula: 